Effects of the Combination of ß-Hydroxy-ß-Methyl Butyrate and R(+) Lipoic Acid in a Cellular Model of Sarcopenia.

: Sarcopenia is a clinical problem associated with several pathological and non-pathological conditions. The aim of the present research is the evaluation of the pharmacological profile of the leucine metabolite ß-hydroxy-ß-methyl butyrate (HMB) associated with the natural R(+) stereoisomer of lipoic acid (R(+)LA) in a cellular model of muscle wasting. The C2C12 cell line is used as myoblasts or is differentiated in myotubes, sarcopenia is induced by dexamethasone (DEX). A Bonferroni significant difference procedure is used for a post hoc comparison. DEX toxicity (0.01-300 µM concentration range) is evaluated in myoblasts to measure cell viability and caspase 3 activation after 24 h and 48 h; cell incubation with 1 µM DEX for 48 h is chosen as optimal treatment for decreasing cell viability and increasing caspase 3 activity. R(+)LA or HMB significantly prevents DEX-induced cell mortality; the efficacy is improved when 100 µM R(+)LA is combined with 1 mM HMB. Regarding myoblasts, this combination significantly reduces DEX-evoked O2- production and protein oxidative damage. During the early phase of myotube formation, the mixture preserves the number of myogenin-positive cells, whereas it completely prevents the DEX-dependent damage in a later phase of myotube differentiation (7 days), as evaluated by cell diameter and percentage of multinucleated cells. R(+)LA in association with HMB is suggested for sarcopenia therapy.

Management of chronic pruritus with a UV filtering topical cream.

Chronic pruritus is a common dermatological condition affecting 10-13% of the general population. UVB phototherapy has been demonstrated to be effective in relieving the symptoms of pruritus. However, phototherapy is rarely administered because the treatment is time-consuming and expensive, when compared to other topical drugs. In previous works, it has been reported that a topical cream, which selectively filters solar UVB can be used as a convenient alternative to traditional phototherapy. Here, we report the results of a pilot study aimed at assessing the effectiveness of the cream for treating pruritus. Seven patients with pruritus symptoms were included in the study. After 3 months of treatment (3 sessions per week), all patients noted improvement in pruritus symptoms. These preliminary results demonstrate that the novel topical cream could provide a convenient, low cost treatment for chronic pruritus patients.

Oxidative, metabolic, and apoptotic responses of Schwann cells to high glucose levels.

The specific response of murine Schwann cells IMS32 to acute and chronic hyperglycemia conditions was evaluated. The pathophysiological alterations were studied to deepening the role of Schwann cells in diabetes-related neurotoxicity and to assess a model to screen new protective molecules. IMS32 were incubated with 30 and 56 mM glucose for 48 h and 7 and 14 days, and markers of oxidative stress, apoptosis, and polyol pathway were evaluated. High glucose induced O(2) -production and lipid peroxidation at all time point whereas Caspase 3 activity was induced only after 14 days. Aldose reductase activity and expression were significantly increased after 48 h and 14 days, respectively. Our results describe the response of Schwann cells to high glucose conditions and suggest the use of IMS32 for the screening of protective molecules in diabetes-induced neuropathy.

In Vitro Evidence for the Use of Astragali Radix Extracts as Adjuvant against Oxaliplatin-Induced Neurotoxicity.

The repeated exposure to the anticancer drug oxaliplatin induces a disabling, painful neuropathy. The current pharmacological treatments are unsatisfactory and unable to modify the complex nervous damage induced by the platin derivative. Recently, we described a system of cellular measures of oxidative stress as a method for studying features of oxaliplatin neurotoxicity and screening new compounds able to reduce oxaliplatin-induced neuropathy. Based on this experimental design, the protective properties of Astragali radix were studied comparing aqueous and two hydroalcoholic root extracts. Aqueous and the 20 % hydroalcoholic (20 % water) extract were prepared from plant material, while the 50 % hydroalcoholic (50 % water) extract was a commercial one. All of the extracts were characterized in terms of drug extract ratio and content of typical isoflavonoids, Astragaloside IV, and related saponins. Furthermore, the molecular weight of the polysaccharide fraction was evaluated by light scattering analysis. Oxaliplatin increased the superoxide anion production both in the neuronal-derived cell line SH-SY5Y and in primary cultures of rat cortical astrocytes. Aqueous and the 50 % hydroalcoholic extract (50 µg/mL) showed significant antioxidant effects. In astrocytes, aqueous and the 50 % hydroalcoholic extract showed protective effects against oxaliplatin-induced lipid peroxidation (malonyl dialdehyde levels), protein (carbonylated proteins), and DNA oxidation (8-OH-2-dG levels). The 50 % hydroalcoholic extract was the most active in preventing the activation of the apoptotic enzyme caspase-3 and it was the only able to stimulate astrocyte viability. None of the tested extracts interfered with the toxicity elicited by oxaliplatin in the human colon adenocarcinoma cell line HT-29. The pharmacological profile of Astragali radix extracts, in particular, the aqueous and 50 % hydroalcoholic extracts, makes these natural products candidates as therapeutic adjuvant agents against oxaliplatin neurotoxicity.

α7 Nicotinic Receptor Promotes the Neuroprotective Functions of Astrocytes against Oxaliplatin Neurotoxicity.

Neuropathies are characterized by a complex response of the central nervous system to injuries. Glial cells are recruited to maintain neuronal homeostasis but dysregulated activation leads to pain signaling amplification and reduces the glial neuroprotective power. Recently, we highlighted the property of α7 nicotinic-acetylcholine-receptor (nAChR) agonists to relieve pain and induce neuroprotection simultaneously with a strong increase in astrocyte density. Aimed to study the role of α7 nAChR in the neuron-glia cross-talk, we treated primary rat neurons and astrocytes with the neurotoxic anticancer drug oxaliplatin evaluating the effect of the α7 nAChR agonist PNU-282987 (PNU). Oxaliplatin (1 µM, 48 h) reduced cell viability and increased caspase-3 activity of neuron monocultures without damaging astrocytes. In cocultures, astrocytes were not able to protect neurons by oxaliplatin even if glial cell metabolism was stimulated (pyruvate increase). On the contrary, the coculture incubation with 10 µM PNU improved neuron viability and inhibited apoptosis. In the absence of astrocytes, the protection disappeared. Furthermore, PNU promoted the release of the anti-inflammatory cytokine TGF-ß1 and the expression of the glutamate-detoxifying enzyme glutamine synthetase. The α7 nAChR stimulation protects neurons from oxaliplatin toxicity through an astrocyte-mediated mechanism. α7 nAChR is suggested for recovering the homeostatic role of astrocytes.

Different apoptotic pathways activated by oxaliplatin in primary astrocytes vs. colo-rectal cancer cells.

Oxaliplatin-based chemotherapy improves the outcomes of metastatic colorectal cancer patients. Its most significant and dose-limiting side effect is the development of a neuropathic syndrome. The mechanism of the neurotoxicity is unclear. The limited knowledge about differences existing between neurotoxic and antitumor effects hinders the discovery of effective and safe adjuvant therapies. In vitro, we suggested cell-specific activation apoptotic pathways in normal nervous cells (astrocytes) vs. colon-cancer cells (HT-29). In the present research we compared the apoptotic signals evoked by oxaliplatin in astrocytes and HT-29 analyzing the intrinsic and extrinsic apoptotic pathways. In astrocytes, oxaliplatin induced a mitochondrial derangement measured as cytosolic release of cytochrome C, increase in superoxide anion levels and decreased expression of the antiapoptotic protein Bcl-2. Caspase-8, a main initiator of the extrinsic process remained unaltered. On the contrary, in HT-29 oxaliplatin increased caspase-8 activity and Bid expression, thus activating the extrinsic apoptosis, while the Bcl-2 increased expression blocked the mitochondrial damage. Data suggest the preferred activation of the intrinsic apoptosis as oxaliplatin damage signaling in normal nervous cells. The extrinsic pathway prevails in tumor cells indicating a possible strategy for planning new molecules to treat oxaliplatin-dependent neurotoxicity without negatively influence chemotherapy.

Pretreatment with Relaxin Does Not Restore NO-Mediated Modulation of Calcium Signal in Coronary Endothelial Cells Isolated from Spontaneously Hypertensive Rats.

We demonstrated that in coronary endothelial cells (RCEs) from normotensive Wistar Kyoto rats (WKY), the hormone relaxin (RLX) increases NO production and reduces calcium transients by a NO-related mechanism. Since an impairment of the NO pathway has been described in spontaneously hypertensive rats (SHR), the present study was aimed at exploring RLX effects on RCEs from SHR, hypothesizing that RLX could restore calcium responsiveness to NO. RCEs were isolated from WKY and SHR. Calcium transients were evaluated by image analysis after the administration of angiotensin II or α-thrombin. Angiotensin II (1 µM) caused a prompt rise of [Ca2+]i in WKY and SHR RCEs and a rapid decrease, being the decay time higher in SHR than in WKY. NOS inhibition increased calcium transient in WKY, but not in SHR RCEs. Whereas RLX pretreatment (24 h, 60 ng/mL) was ineffective in SHR, it strongly reduced calcium transient in WKY in a NO-dependent way. A similar behavior was measured using 30 U/mL α-thrombin. The current study offers evidence that RLX cannot restore NO responsiveness in SHR, suggesting an accurate selection of patients eligible for RLX treatment of cardiovascular diseases.

Vitiligo: what's new in the psycho-neuro-endocrine-immune connection and related treatments.

Vitiligo is an acquired depigmentary skin disorder of unknown origin characterized by well-demarcated, white macules of varying size and distribution. Despite relevant new research and progresses, why melanocytes disappear to induce the characteristic achromic lesions of vitiligo is not fully understood. In spite of recent findings implicating genetic, immune and oxidative stress factors, the exact pathogenesis of vitiligo remains obscure. An innovative concept based on a functional cross-talk between the nervous and immune system is emerging. Neuropeptides released from peripheral nerve endings could synergize with new cytokines to adversely affect melanocyte function and viability. Evidence is increasing regarding the role of neuropeptides in the pathogenesis of vitiligo and a new winning approach to vitiligo therapy based on neuropeptides regulation is at the horizon.

BDNF and Artemin are increased in drug-naïve non-depressed GAD patients: preliminary data.

OBJECTIVE: While the role of neuronal and glial plasticity are well established in the pathophysiology of mood disorders, the pattern and measures of neuronal and glial cell line-derived neurotrophic factors are unknown in generalized anxiety disorder (GAD). The present study evaluates brain-derived neurotrophic factor (BDNF) and Artemin (ARTN) plasma levels in GAD patients. METHODS: Fourteen drug-naïve GAD patients without major depression were enrolled and plasmatic levels of BDNF and ARTN mRNA were measured by RT-PCR, and compared to matched healthy controls. RESULTS: The results showed an unexpected increase in mRNA levels of both BDNF and ARTN in patients with GAD, that appeared almost doubled when compared to healthy controls. In comparison, both BDNF and ARTN are reduced in patients with major depressive disorder. Further, the results are intriguing and might involve distinguishing pathophysiological pathways. CONCLUSIONS: This is the first report of increased levels of a neurotrophic factor and of a glial cell line-derived neurotrophic factor family member in GAD patients. While further studies to confirm these results and the functional meaning in terms of pathophysiology of GAD are needed, the potential conceptual and clinical meanings are discussed.

Low dose native type II collagen prevents pain in a rat osteoarthritis model.

BACKGROUND: Osteoarthritis is the most widespread joint-affecting disease. Patients with osteoarthritis experience pain and impaired mobility resulting in marked reduction of quality of life. A progressive cartilage loss is responsible of an evolving disease difficult to treat. The characteristic of chronicity determines the need of new active disease modifying drugs. Aim of the present research is to evaluate the role of low doses of native type II collagen in the rat model of osteoarthritis induced by sodium monoiodoacetate (MIA). METHODS: 1, 3 and 10 mg kg-1 porcine native type II collagen were daily per os administered for 13 days starting from the day of MIA intra-articular injection. RESULTS: On day 14, collagen-treated rats showed a significant prevention of pain threshold alterations induced by MIA. Evaluation were performed on paws using mechanical noxious (Paw pressure test) or non-noxious (Electronic Von Frey test) stimuli, and a decrease of articular pain was directly measured on the damaged joint (PAM test). The efficacy of collagen in reducing pain was as higher as the dose was lowered. Moreover, a reduced postural unbalance, measured as hind limb weight bearing alterations (Incapacitance test), and a general improvement of motor activity (Animex test) were observed. Finally, the decrease of plasma and urine levels of CTX-II (Cross Linked C-Telopeptide of Type II Collagen), a biomarker of cartilage degradation, suggests a collagen-dependent decrease of structural joint damage. CONCLUSIONS: These results describe the preclinical efficacy of low dosages of native type II collagen as pain reliever by a mechanism that involves a protective effect on cartilage.

Calcitonin gene-related peptide-mediated enhancement of purinergic neuron/glia communication by the algogenic factor bradykinin in mouse trigeminal ganglia from wild-type and R192Q Cav2.1 Knock-in mice: implications for basic mechanisms of migraine pain.

Within the trigeminal ganglion, crosstalk between neurons and satellite glial cells (SGCs) contributes to neuronal sensitization and transduction of painful stimuli, including migraine pain, at least partly through activation of purinergic receptor mechanisms. We previously showed that the algogenic mediator bradykinin (BK) potentiates purinergic P2Y receptors on SGCs in primary trigeminal cultures. Our present study investigated the molecular basis of this effect in wild-type (WT) mice and Ca(V)2.1 α1 R192Q mutant knock-in (KI) mice expressing a human mutation causing familial hemiplegic migraine type 1. Single-cell calcium imaging of WT cultures revealed functional BK receptors in neurons only, suggesting a paracrine action by BK to release a soluble mediator responsible for its effects on SGCs. We identified this mediator as the neuropeptide calcitonin gene-related peptide (CGRP), whose levels were markedly increased by BK, while the CGRP antagonist CGRP(8-37) and the anti-migraine drug sumatriptan inhibited BK actions. Unlike CGRP, BK was ineffective in neuron-free SGC cultures, confirming the CGRP neuronal source. P2Y receptor potentiation induced by CGRP in SGCs was mediated via activation of the extracellular signal-regulated kinase 1/2 pathways, and after exposure to CGRP, a significant release of several cytokines was detected. Interestingly, both basal and BK-stimulated CGRP release was higher in KI mouse cultures, where BK significantly upregulated the number of SGCs showing functional UTP-sensitive P2Y receptors. Our findings suggest that P2Y receptors on glial cells might be considered as novel players in the cellular processes underlying migraine pathophysiology and might represent new targets for the development of innovative therapeutic agents against migraine pain.

Temporomandibular joint inflammation activates glial and immune cells in both the trigeminal ganglia and in the spinal trigeminal nucleus.

BACKGROUND: Glial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS). Indeed, glial cell activation has been reported in both the dorsal root ganglia and the spinal cord following injury or inflammation of the sciatic nerve, but no data are currently available in animal models of trigeminal sensitization. Therefore, in the present study, we evaluated glial cell activation in the trigeminal-spinal system following injection of the Complete Freund's Adjuvant (CFA) into the temporomandibular joint, which generates inflammatory pain and trigeminal hypersensitivity. RESULTS: CFA-injected animals showed ipsilateral mechanical allodynia and temporomandibular joint edema, accompanied in the trigeminal ganglion by a strong increase in the number of GFAP-positive satellite glial cells encircling neurons and by the activation of resident macrophages. Seventy-two hours after CFA injection, activated microglial cells were observed in the ipsilateral trigeminal subnucleus caudalis and in the cervical dorsal horn, with a significant up-regulation of Iba1 immunoreactivity, but no signs of reactive astrogliosis were detected in the same areas. Since the purinergic system has been implicated in the activation of microglial cells during neuropathic pain, we have also evaluated the expression of the microglial-specific P2Y12 receptor subtype. No upregulation of this receptor was detected following induction of TMJ inflammation, suggesting that any possible role of P2Y12 in this paradigm of inflammatory pain does not involve changes in receptor expression. CONCLUSIONS: Our data indicate that specific glial cell populations become activated in both the trigeminal ganglia and the CNS following induction of temporomandibular joint inflammation, and suggest that they might represent innovative targets for controlling pain during trigeminal nerve sensitization.

Adipose-derived stem cells decrease pain in a rat model of oxaliplatin-induced neuropathy: Role of VEGF-A modulation.

Oxaliplatin therapy of colorectal cancer induces a dose-dependent neuropathic syndrome in 50% of patients. Pharmacological treatments may offer limited relief; scientific efforts are needed for new therapeutic approaches. Therefore we evaluated in a preclinical setting the pain relieving properties of mesenchymal stem cells and its secretome. Rat adipose stem cells (rASCs) were administered in a rat model of oxaliplatin-induced neuropathy. A single intravenous injection of rASCs reduced oxaliplatin-dependent mechanical hypersensitivity to noxious and non-noxious stimuli taking effect 1 h after administration, peaking 6 h thereafter and lasting 5 days. Cell-conditioned medium was ineffective. Repeated rASCs injections every 5 days relieved pain each time with a comparable effect. Labeled rASCs were detected in the bloodstream 1 and 3 h after administration and found in the liver 24 h thereafter. In oxaliplatin-treated rats, the plasma concentration of vascular endothelial growth factor (pan VEGF-A) was increased while the isoform VEGF165b was upregulated in the spinal cord. Both alterations were reverted by rASCs. The anti-VEGF-A monoclonal antibody bevacizumab (intraperitoneally) reduced oxaliplatin-dependent pain. Studying the peripheral and central role of VEGF165b in pain, we determined that the intraplantar and intrathecal injection of the growth factor induced a pro-algesic effect. In the oxaliplatin neuropathy model, the intrathecal infusion of bevacizumab, anti-rat VEGF165b antibody and rASCs reduced pain. Adult adipose mesenchymal stem cells could represent a novel approach in the treatment of neuropathic pain. The regulation of VEGF-A is suggested as an effective mechanism in the complex response orchestrated by stem cells against neuropathy.

Impetiginized Dyshidrotic Eczema.

A 16 years old female patient, affected by atopic dermatitis and rhinoconjunctivitis allergica since childhood, requested a dermatologic consultation for lesions which had appeared after 3 months of local treatment with clobethasole propionate. The histological analysis confirmed the diagnosis of dyshidrotic eczema and the microbiological smears demonstrated a significant infection with Staphylococcus aureus. The risk of developing corticosteroids' side-effects depends on the potency of the product, extended period of use and the volume of product applied. Clobetasol propionate is a group I- highly potent corticosteroid, which should be used for a maximum period of 2 weeks. Several authors have found that this agent has cumulative depot effect, persisting in the epidermis for 4 days after only one application. Taking together these observations, sustained by the clinical case presented above, we can conclude that the infectious risks associated with topical corticosteroid treatment must not be neglected, particularly since treated patients are fragile, and frequently have multiple well-known risk factors.

Lichen Simplex Chronicus as an Essential Part of the Dermatologic Masquerade.

A 48 years old female patient had been suffering from the lesions presented for four years. They have started as small, pruritic patches which had been mechanically irritated and grew up in time. The patient had no associated comorbidities or allergies, and she was not under any medication. On physical examination, she presented one erythematous, exudative plaque, with dimensions of 2.5/4 cm, located on the proximal phalanx and interphalangeal articulation of the left thumb. All histopathological features were consistent with the diagnosis of lichen simplex chronicus. Some lesions of lichen simplex chronicus exhibit signs of pseudocarcinomatous, infundibular and sometimes eccrine ductal proliferation of keratinocytes. Although the pseudoinfiltrative aspect of the epithelial proliferation and its pronounced degree might mimic a well-differentiated lesion of squamous cell carcinoma, a lack of cellular atypia and atypical mitotic figures are features that do not support this diagnosis. On the other hand, long lasting lesions of lichen simplex chronicus may lead to alterations in the processes of keratinocyte proliferation and differentiation and eventually give rise to malignant transformation. The best treatment management is a psychodermatological approach, a combination of skin care with psychotherapy, in order to prevent relapses.

Astragali radix: could it be an adjuvant for oxaliplatin-induced neuropathy?

Neurotoxicity is a major side effect of platinum derivatives both during and after treatment. In the absence of effective pharmacological compounds, the opportunity to identify safe adjuvant treatments among medicinal plants seems appropriate. Astragali radix is an adaptogenic herbal product recently analyzed in platinum-treated cancer patients. With the aim of evaluating the anti-neuropathic profile of Astragali radix, a previously characterized aqueous (Aqu) and two hydroalcoholic (20%HA and 50%HA) extracts were tested in a rat model of oxaliplatin-induced neuropathy. Repeated administrations significantly reduced oxaliplatin-dependent hypersensitivity with 50%HA, the most effective, fully preventing mechanical and thermal hypersensitivity. Ex vivo, 50%HA reduced morphometric and molecular alterations induced by oxaliplatin in peripheral nerve and dorsal-root-ganglia. In the spinal cord and in brain areas, 50%HA significantly decreased activation of microglia and astrocytes. Furthermore, 50%HA prevented the nephro- and hepato-toxicity induced by the anticancer drug. The protective effect of 50%HA did not alter oxaliplatin-induced apoptosis in colon tumors of Pirc rats, an Apc-driven model of colon carcinogenesis. The hydroalcoholic extract (50%HA) of Astragali radix relieves pain and promotes the rescue mechanisms that protect nervous tissue from the damages triggering chronic pain. A safe profile strongly suggests the usefulness of this natural product in oxaliplatin-induced neuropathy.

Role of Nitric Oxide, Nitric Oxide Synthase, Soluble Guanylyl Cyclase, and cGMP-Dependent Protein Kinase I in Mouse Stem Cell Cardiac Development.

Introduction and Aim. Nitric oxide (NO) can trigger cardiac differentiation of embryonic stem cells (ESCs), indicating a cardiogenic function of the NO synthetizing enzyme(s) (NOS). However, the involvement of the NO/NOS downstream effectors soluble guanylyl cyclase (sGC) and cGMP activated protein kinase I (PKG-I) is less defined. Therefore, we assess the involvement of the entire NO/NOS/sGC/PKG-I pathway during cardiac differentiation process. Methods. Mouse ESCs were differentiated toward cardiac lineages by hanging drop methodology for 21 days. NOS/sGC/PKG-I pathway was studied quantifying genes, proteins, enzymatic activities, and effects of inhibition during differentiation. Percentages of beating embryoid bodies (mEBs) were evaluated as an index of cardiogenesis. Results and Discussion. Genes and protein expression of enzymes were increased during differentiation with distinctive kinetics and proteins possessed their enzymatic functions. Exogenous administered NO accelerated whereas the blockade of PKG-I strongly slowed cardiogenesis. sGC inhibition was effective only at early stages and NOS blockade ineffective. Of NOS/sGC/PKG-I pathway, PKG-I seems to play the prominent role in cardiac maturation. Conclusion. We concluded that exogenous administered NO and other pharmacological strategies able to increase the activity of PKG-I provide new tools to investigate and promote differentiation of cardiogenic precursors.

Effect of the SOD mimetic MnL4 on in vitro and in vivo oxaliplatin toxicity: Possible aid in chemotherapy induced neuropathy.

BACKGROUND: One of the most discomfortable dose-limiting adverse reactions of effective drugs for the treatment of solid tumors is a peripheral neuropathy which is the main reason for dose reduction and discontinuation of the therapy. We identified oxidative stress as one target of oxaliplatin toxicity in the search of possible adjuvant therapies to prevent neuropathy and alleviate pain. Therefore, we studied an effective SOD mimetic compound, MnL4, as a possible adjuvant treatment in in vitro cellular cultures and in vivo on a rat model of oxaliplatin-induced neuropathy. METHODS AND RESULTS: All rat manipulations were carried out according to the European Community guidelines for animal care. We performed experiments on SH-SY5Y, HT-29 and primary cortical rat astrocytes. Incubation with 100 µM oxaliplatin increased superoxide anion production and caspase 3/7 activity in the neuronal cell line SH-SY5Y and cortical astrocytes. MnL4 (10 µM) significantly reduced the increase in superoxide anion in both cell types, but prevented caspase 3/7 activity only in astrocytes. MnL4 reduced lipid peroxidation induced by oxaliplatin and normalized the intracellular calcium signal evoked by ATP and acetylcholine in astrocytes, preincubated with oxaliplatin. MnL4 did not interfere with the concentration- and time-dependent cytotoxic effects of oxaliplatin on the cancer cell lines HT-29 and LoVo. In vivo MnL4 reduced the response at mechanical noxious and mechanical and thermal non-noxious stimuli in oxaliplatin treated animals. Rat rota-rod performances were improved. CONCLUSION: Since MnL4 exerts its beneficial effects without interfering with the anticancer activity of oxaliplatin, it could be proposed as adjuvant to prevent and reduce oxaliplatin induced neuropathy.

Widespread pain reliever profile of a flower extract of Tanacetum parthenium.

BACKGROUND: Tanacetum parthenium L., commonly called Feverfew, is known for anti-inflammatory and anti-migraine properties. PURPOSE: Aimed to individuate new therapeutical strategies to control acute and persistent pain induced by different origins we tested two hydroalcoholic extracts obtained from Feverfew flowers and leaves, respectively. STUDY DESIGN: Extracts were characterized according to the European Pharmacopoeia monograph. Both the extracts were tested after acute per os administration in the dose range 30-1000 mg kg(-1). The anti-nociceptive properties were evaluated by the Writhing test in mice. RESULTS: The number of abdominal contractions was dose dependently reduced by the flower extract. It reduced mechanical hypersensitivity (Paw pressure test) related to the acute inflammatory phase induced by carrageenan similarly to diclofenac and ibuprofen. In the osteoarthritis model induced by intra articular injection of monoiodoacetate (MIA) the flower extract significantly increased the pain threshold peaking 30 min after treatment. Moreover, it was effective in the chronic constriction injury model of neuropathic pain showing activity similar to the anti-epileptic drug gabapentin. The flower extract activity was confirmed in rat models of chemotherapy-induced neuropathic pain. The mechanical hypersensitivity induced by repeated treatments with the anticancer drug oxaliplatin and with the antiviral dideoxycytidine was significantly reduced after a single injection of Feverfew flower extract. The leaf extract showed lesser efficacy and potency and it was devoid of any effect in carrageenan-, MIA- and chemotherapy-induced pain. CONCLUSION: The present Feverfew flower extract behaves as a potent pain reliever in acute, inflammatory, articular and neuropathic pain. It appears as a natural strategy potentially suitable for the treatment of different kinds of pain.